Replication protein A (RPA) is a key component of the DNA replication and repair machineries. RPA is a single stranded DNA binding protein that interacts with DNA replication origin binding proteins, DNA polymerases, transcription activator proteins and DNA repair factors, including those that are mutated in several forms of human cancer. RPA is a heterotrimer; the DNA binding domain has been localized to the largest subunit. We have used limited proteolysis and deletion analysis to identify the minimal single strand DNA binding domain. We have crystallized this domain together with ssDNA. We are pursuing heavy atom searches on our unit and have also prepared selenomethionine-labeled protein for co-crystallization.